Evidence map›Paper›PMID 34078425›Full record

ArticleMolecular neurodegeneration2021

Parkinson mice show functional and molecular changes in the gut long before motoric disease onset.

Manuela Gries, Anne Christmann, Steven Schulte, Maximilian Weyland, Stephanie Rommel, Monika Martin, Marko Baller, Ralph Röth, Stefanie Schmitteckert, Marcus Unger and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

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  11. Gastrointestinal dysmotility in rodent models of Parkinson's disease.American journal of physiology. Gastrointestinal and liver physiology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 3 countries.

Manuela Gries *Department of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Anne Christmann *Department of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Steven SchulteDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Maximilian WeylandDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Stephanie RommelDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Monika MartinDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Marko BallerDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany.
Ralph RöthDepartment of Human Molecular Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
Stefanie SchmitteckertDepartment of Human Molecular Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
Marcus UngerDepartment of Neurology, Saarland University, 66421, Homburg, Germany.
Yang LiuDepartment of Neurology, Saarland University, 66421, Homburg, Germany.
Frederik SommerMolecular Biotechnology and Systems Biology, University of Kaiserslautern, 67663, Kaiserslautern, Germany.
Timo MühlhausComputational Systems Biology, University of Kaiserslautern, 67663, Kaiserslautern, Germany.
Michael SchrodaMolecular Biotechnology and Systems Biology, University of Kaiserslautern, 67663, Kaiserslautern, Germany.
Jean-Pierre TimmermansLaboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, 2610, Antwerp, Belgium.
Isabel PintelonLaboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, 2610, Antwerp, Belgium.
Gudrun A RappoldDepartment of Human Molecular Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
Markus BritschgiRoche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Medicine Area, Neuroscience Discovery, Roche Innovation Center Basel, 4070, Basel, Switzerland.
Hilal LashuelLaboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
Michael D MengerInstitute for Clinical & Experimental Surgery, Faculty of Medicine, Saarland University, 66421, Homburg, Germany.
Matthias W LaschkeInstitute for Clinical & Experimental Surgery, Faculty of Medicine, Saarland University, 66421, Homburg, Germany.
Beate NieslerDepartment of Human Molecular Genetics, University of Heidelberg, 69120, Heidelberg, Germany.
Karl-Herbert SchäferDepartment of Informatics and Microsystems and Technology, University of Applied Science Kaiserslautern, Working Group Enteric Nervous System, 66482, Zweibrücken, Germany. karlherbert.schaefer@hs-kl.de.ORCID 0000-0002-4724-813X
University of Applied Sciences Kaiserslautern · DEHeidelberg University · DESaarland University · DEUniversity of Kaiserslautern · DEUniversity of Antwerp · BEÉcole Polytechnique Fédérale de Lausanne · CHRoche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThere is increasing evidence that Parkinson's disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain is already destroyed, so that the lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use a transgenic A30P-α-synuclein-overexpressing PD mouse model to identify appropriate candidate markers in the gut before hallmark symptoms begin to manifest.

methodsBased on a gait analysis and striatal dopamine levels, we defined 2-month-old A30P mice as pre-symptomatic (psA30P), since they are not showing any motoric impairments of the skeletal neuromuscular system and no reduced dopamine levels, but an intestinal α-synuclein pathology. Mice at this particular age were further used to analyze functional and molecular alterations in both, the gastrointestinal tract and the ENS, to identify early pathological changes. We examined the gastrointestinal motility, the molecular composition of the ENS, as well as the expression of regulating miRNAs. Moreover, we applied A30P-α-synuclein challenges in vitro to simulate PD in the ENS.

resultsA retarded gut motility and early molecular dysregulations were found in the myenteric plexus of psA30P mice. We found that i.e. neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are significantly altered in the psA30P, thus representing potential biomarkers for early PD. Many of the dysregulated miRNAs found in the psA30P mice are reported to be changed in PD patients as well, either in blood, cerebrospinal fluid or brain tissue. Interestingly, the in vitro approaches delivered similar changes in the ENS cultures as seen in the transgenic animals, thus confirming the data from the mouse model.

conclusionsThese findings provide an interesting and novel approach for the identification of appropriate biomarkers in men.

Indexed as

Prodromal SymptomsAnimalsEnteric Nervous SystemGastrointestinal DiseasesGastrointestinal MotilityMiceMice, Inbred C57BLParkinsonian DisordersEarly onsetEnteric nervous systemGastrointestinal motilityParkinson’s diseaseProtein-and miRNA biomarkers

Identifiers

PMID34078425
PMCPMC8170976
OpenAlexW3119201419

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.